PROJECT SUMMARY/ABSTRACT The Untargeted Analysis Resource Core (UARC) of the RTI CHEAR Hub will provide untargeted broad spectrum analysis of cells, excreta, fluids, or tissue extracts obtained through the CHEAR Network or in collaboration with the Development Core (DC). The UARC will support the RTI CHEAR Hub by providing standardized analysis and data in a consistent and coherent format and providing expertise for interpreting results in the context of the study design and other phenotypic measures. The UARC will consult with the RTI CHEAR Hub Management Team (MT) and, as appropriate, the CHEAR Coordinating Center and the CHEAR clients to participate in study design and selection of methods. The UARC will use nuclear magnetic resonance (NMR) and mass spectrometry (MS) metabolomics to generate profiles of endogenous and exogenous compounds in biospecimens using standardized methods that have been developed by two NIH Common Fund (NIH C-F) Regional Comprehensive Metabolomics Cores (RCMRC) located at RTI and at the University of California at Davis. We will conduct comparative analysis of data using the phenotypic information provided, such as comparison of high versus low exposure, cases versus controls, or obese versus healthy weight. We will determine features that are important to defining the study phenotype(s) being investigated and match features to in-house and public libraries for compound assignment. The UARC will determine features of unknowns and prioritize signals for complete characterization and will work with the NIH C-F Metabolite Standards Synthesis Core (MSSC) to determine mass and isotopic-labeled compounds needed to confirm proposed biomarkers. The UARC will also use methods to evaluate panels of markers (e.g., endocannabinoids, neurotransmitters, lipids, metallomics, mineralomics, and microbial metabolites). We will take similar approaches using proteomics methods, if the needs arise. We will work with the Development Core to establish new data capture or analysis methods for new targeted methods based on hits from the untargeted approaches, to increase coverage, and to identify unknowns. The UARC will be in close communication with the RTI CHEAR Hub MT, and the UARC Core Leader will serve on the CHEAR Steering Committee. The UARC will ensure that data are transferred to the CHEAR Data Repository and Analysis Science Center. The UARC will ensure cost-effective approaches are used by analyzing samples in appropriate size batches, by developing and following well-defined statements of work, and by using template reporting processes. The UARC will participate in designing and conducting ring trials, as appropriate, to assess the ability to detect and quantitate spiked standards and to make comparisons among different study phenotypes using UARC methods.